Much emphasis has been placed on the role of plasma fibronectin (PFn) as a coagulation factor, and its consumption/catabolism during pathophysiological conditions such as the acute-phase response following trauma or injury. Recently, interest has focussed on the maintenance of normal circulating levels of PFn that would preserve maximal function of the mononuclear phagocytic system and its participation in fibroblast infiltration and wound healing. Whether or not this is an accurate or complete representation of the role of PFn, little is known about anabolic mechanisms that maintain or restore PFn and other acute-phase proteins to normal circulating levels. Recent studies have found elevated levels of glucocorticoids and cytokines such as hepatocyte stimulating factor following experimentally induced inflammation in several organisms. These factors also stimulate PFn (and other acute-phase protein) production in vitro and/or in vivo, and are therefore implicated in mechanisms that restore or maintain normal levels of circulating PFn. The specific aims of the proposed studies are: 1) to investigate the effects of glucocorticoids (dexamethasone, corticosterone) and a purified recombinant interleukin-6 (rIL-6) alone and in concert on PFn and PFn mRNA transcription in a chick hepatocyte culture model system, and 2) to correlate in vitro changes in levels of PFn production with the effects of these factors in vivo. PFn will be assayed by rocket or ELISA immunoassay. PFn mRNA levels will be measured (and distinguished from cell-associated Fn, a protein differentially processed from the same pre-mRNA transcript as PFn) by Sl nuclease assay. Nuclear run-off studies are proposed to measure the effects of glucocorticoids and rIL-6 on Fn transcription rates. Finally, the timing and magnitude of the effects of these factors will be determined in vivo and correlated with their effects on cultured hepatocytes.